Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Research & Development Service, John D. Dingell VA Medical Center, Detroit, MI 48201, USA; Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Life Sci. 2014 Feb 27;97(1):31-6. doi: 10.1016/j.lfs.2013.07.015. Epub 2013 Jul 24.
Mephedrone is a stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA). Although mephedrone does not damage dopamine nerve endings it increases the neurotoxicity of amphetamine, methamphetamine and MDMA. The effects of mephedrone on serotonin (5HT) nerve endings are not fully understood, with some investigators reporting damage while others conclude it does not. Presently, we investigate if mephedrone given alone or with methamphetamine or MDMA damages 5HT nerve endings of the hippocampus.
The status of 5HT nerve endings in the hippocampus of female C57BL mice was assessed through measures of 5HT by HPLC and by immunoblot analysis of serotonin transporter (SERT) and tryptophan hydroxylase 2 (TPH2), selective markers of 5HT nerve endings. Astrocytosis was assessed through measures of glial fibrillary acidic protein (GFAP) (immunoblotting) and microglial activation was determined by histochemical staining with Isolectin B4.
Mephedrone alone did not cause persistent reductions in the levels of 5HT, SERT or TPH2. Methamphetamine and MDMA alone caused mild reductions in 5HT but did not change SERT and TPH2 levels. Combined treatment with mephedrone and methamphetamine or MDMA did not change the status of 5HT nerve endings to an extent that was different from either drug alone.
Mephedrone does not cause toxicity to 5HT nerve endings of the hippocampus. When co-administered with methamphetamine or MDMA, drugs that are often co-abused with mephedrone by humans, toxicity is not increased as is the case for dopamine nerve endings when these drugs are taken together.
麦角酸二乙酰胺是一种滥用兴奋剂，与甲基苯丙胺和 3,4-亚甲基二氧甲基苯丙胺（MDMA）具有密切的结构和机制相似性。尽管麦角酸二乙酰胺不会破坏多巴胺神经末梢，但它会增加安非他命、甲基苯丙胺和 MDMA 的神经毒性。麦角酸二乙酰胺对 5-羟色胺（5HT）神经末梢的影响尚未完全了解，一些研究人员报告说它会造成损害，而另一些研究人员则得出结论认为它不会造成损害。目前，我们研究麦角酸二乙酰胺单独或与甲基苯丙胺或 MDMA 一起是否会损害海马体的 5HT 神经末梢。
通过高效液相色谱法测量 5HT 和免疫印迹分析 5HT 神经末梢的选择性标志物 5-羟色胺转运体（SERT）和色氨酸羟化酶 2（TPH2），评估雌性 C57BL 小鼠海马体中 5HT 神经末梢的状态。通过胶质纤维酸性蛋白（GFAP）（免疫印迹）测量星形胶质细胞增生，并通过异硫氰酸荧光素 B4 组织化学染色确定小胶质细胞激活。
麦角酸二乙酰胺单独使用不会导致 5HT、SERT 或 TPH2 水平持续降低。甲基苯丙胺和 MDMA 单独使用会导致 5HT 轻度减少，但不会改变 SERT 和 TPH2 水平。麦角酸二乙酰胺与甲基苯丙胺或 MDMA 联合治疗不会使 5HT 神经末梢的状态发生改变，其程度与单独使用任何一种药物都不同。
麦角酸二乙酰胺不会导致海马体 5HT 神经末梢中毒。当与甲基苯丙胺或 MDMA 一起服用时，这些药物通常是人类与麦角酸二乙酰胺一起滥用的药物，与多巴胺神经末梢一起服用时，神经毒性不会增加。
